Comparison of serum cholesterol levels in a matched case-control study indicates that patients with colon cancer have serum cholesterol levels lower than those of controls. In 133 pairs matched by age and sex, serum cholesterol levels were 188 +/- 42 mg/dl for cases and 213 +/- 42 mg/dl for controls (paired t-test = 5.08; P less than 0.001). Following stratification by tumor stage, significant differences in serum cholesterol levels persisted between cases with advanced tumors (Duke's classification C1, C2, and D) and controls (mean serum cholesterol difference, 41 +/- 41 mg/dl; paired t-test = 6.16; P less than 0.001) but not between cases with early tumors (Duke's classification A, B1, and B2) and controls, although the same trend was noted. Matching of 130 early tumors to advanced tumors showed that women, but not men, had a significantly lower serum cholesterol level with advancing disease. The findings support the concept that low serum cholesterol levels observed in colon cancer patients may be the result of the metabolic influence of advanced tumors, at least in women, and may not necessarily precede tumor formation.